Extended-spectrum Beta-lactamases: A Brief Clinical Update

Beta-lactamase enzymes (BLs) have become the most worrisome mediators of antimicrobial resistance expressed by gram-negative bacteria (GNB). The multiple families of BLs have in common the ability to hydrolyze the -lactam rings of one or more members of the penicillins, cephalosporins, cephamycins, carbapenems, and monobactams. Extended-spectrum -lactamases (ESBLs) are a subset of BLs that confer resistance to penicillins, cephalosporins, and monobactams and are less efficiently antagonized by -lactamase inhibitors such as clavulanate, sulbactam, and tazobactam. ESBL-producing GNB (ESBL GNB) remain susceptible to the carbapenems and cephamycins (eg, cefoxitin). BLs produce the majority of antimicrobial resistance in GNB, with 1000 identified and more discovered yearly. The following 2 classification systems are used to categorize BLs: the Ambler molecular classes and the Bush-Jacoby Groups. Ambler classes organize BLs based on amino acid sequence motifs. Bush-Jacoby Groups are based on functional characteristics (ie, spectrum of beta-lactams hydrolyzed). The first BLs recognized conferred resistance to penicillins and first-generation cephalosporins. Selective pressure from use of secondand third-generation cephalosporins in the 1980s led to emergence of new versions of BLs with new and often broader resistance profiles. ESBLs represent some of these. These BL genes were originally located on bacterial chromosomes, but have become mobilized on plasmids, enabling easy transfer between bacterial species. These plasmids often carry genes conferring resistance to other antimicrobial agents. ESBL GNB thus often exhibit simultaneous resistance to fluoroquinolones, aminoglycosides, tetracyclines, and trimethoprimsulfamethoxazole.